Proinflammatory Microenvironment in Adenocarcinoma Tissue of Colorectal Carcinoma

• Published in: International journal of molecular sciences 2024-09, Vol.25 (18), p.10062
• Main Authors: Todorović, Slobodan, Ćeranić, Miljan S, Tošković, Borislav, Diklić, Miloš, Mitrović Ajtić, Olivera, Subotički, Tijana, Vukotić, Milica, Dragojević, Teodora, Živković, Emilija, Oprić, Svetlana, Stojiljkovic, Miodrag, Gačić, Jasna, Čolaković, Nataša, Crnokrak, Bogdan, Čokić, Vladan P, Đikić, Dragoslava
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2'-Deoxyguanosine - metabolism; Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adult; Aged; Antigens; beta Catenin - genetics; beta Catenin - metabolism; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cell growth; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Creatinine; Development and progression; Female; Gene expression; Health aspects; Hemoglobin; Heparan sulfate; Humans; Immune response; Inflammation; Inflammation - metabolism; Inflammation - pathology; Interleukin-6 - genetics; Interleukin-6 - metabolism; Male; Medical prognosis; Metastasis; Middle Aged; Mucin-2 - genetics; Mucin-2 - metabolism; NF-kappa B - metabolism; Oxidative Stress; Physiological aspects; Prognosis; Proteins; Signal Transduction; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Tumor markers; Tumor Microenvironment; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251810062

Cancer-promoting proinflammatory microenvironment influences colorectal cancer (CRC) development. We examined the biomarkers of inflammation, intestinal differentiation, and DNA activity correlated with the clinical parameters to observe progression and prognosis in the adenocarcinoma subtype of CRC. Their immunohistology, immunoblotting, and RT-PCR analyses were performed in the adenocarcinoma and neighboring healthy tissues of 64 patients with CRC after routine colorectal surgery. Proinflammatory nuclear factor kappa B (NFκB) signaling as well as interleukin 6 (IL-6) and S100 protein levels were upregulated in adenocarcinoma compared with nearby healthy colon tissue. In contrast to nitrotyrosine expression, the oxidative stress marker 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was increased in adenocarcinoma tissue. Biomarkers of intestinal differentiation β-catenin and mucin 2 (MUC2) were inversely regulated, with the former upregulated in adenocarcinoma tissue and positively correlated with tumor marker CA19-9. Downregulation of MUC2 expression correlated with the increased 2-year survival rate of patients with CRC. Proliferation-related mammalian target of rapamycin (mTOR) signaling was activated, and Ki67 frequency was three-fold augmented in positive correlation with metastasis and cancer stage, respectively. Conclusion: We demonstrated a parallel induction of oxidative stress and inflammation biomarkers in adenocarcinoma tissue that was not reflected in the neighboring healthy colon tissue of CRC. The expansiveness of colorectal adenocarcinoma was confirmed by irregular intestinal differentiation and elevated proliferation biomarkers, predominantly Ki67. The origin of the linked inflammatory factors was in adenocarcinoma tissue, with an accompanying systemic immune response.